Many patients have total brain volume deficits of as much as 14 ccs compared to healthy controls—that’s about a spoonful.”
Dr. Kahn: What does a spoon have to do with schizophrenia?
We’ve come to understand over the last decades that schizophrenia is a brain disease—and that the changes in the brain get worse over time.
Tracy: I named Michael even before he was born. It was like I knew who he was. He was happy and always wanting to do things—just so full of life.
It started mainly in high school. He just was not doing good at all. The grades-he wasn’t showing up, he was acting out. He was drinking. I could see it in his eyes. I knew something had changed.
Michael: I actually had thought my mom had gotten a letter in the mail from the government saying that, you know, we can allow you to kill your son if you’d like to. This is what I believed, and I didn’t think I was wrong.
Sean: To see someone slip away from me like that or slip away from reality—is so sad.
Tracy: It’s scary.
Dr. Kahn: The spoon signifies the difference in brain size between the patient with schizophrenia and the general population and that’s about 14 ccs, which is 1% of our total brain volume. We don’t exactly know whether we can stop the progress of the brain changes. But we do know that certain interventions minimize these brain changes over time.
Michael: My mom, she didn’t really know what was going on, because I never really told her anything so that’s when I started to run away because whenever I would try to explain it-um-she didn’t really understand. And that’s when I would get really angry with her. And then I started having to go to the hospital because, you know, I was hurting myself and threatening to kill myself. And actually, trying to kill myself.
Dr. Kahn: It’s very important that we intervene as early as we can because if we can prevent psychosis, or relapses, or hospitalizations, the outcome is going to be better. So, we can’t wait, and certainly can’t wait 1 or 2 years.
Tracy: So, what I’m learning is that schizophrenia can progress. It gets worse if it’s not treated. So, treatment was crucial, you know the right medicine, family support, plus the therapy. But it was getting him to know this to accept the help, which is a big deal for someone who has schizophrenia.
Michael: I have some coffee made.
Tracy: Ok, good.
Michael: My mom has always been such a positive person. Basically, when things were going wrong she was there to be the positive one. She always said, don’t worry about it, nobody’s trying to hurt you, you know, and things like that.
Tracy: I want him to have short-term goals and long-term goals. So, we wanted to make a board with, you know, just daily tasks and simple reminders.
Dr. Kahn: The family of a patient with schizophrenia is an essential part of the treatment. It used to be, a generation ago, that the family was excluded. They first need to know what the illness is. Very often they don’t understand what it is all about. And they need to understand how important their role is in supporting the patient.
Michael: You know watching these things go makes my day better. Something about just seeing them go—everything’s alright again.
Tracy: I want nothing but good for my son. I want to be there for him unconditionally. That’s what we do for Michael.
Sean: Oh, I’m so proud of Michael now. I’ve always been proud of my brother. He has to work a lot harder than most people and it’s nothing that is his fault. He’s great.
Michael: Well, where I’m at right now - I’m with my family. I’m with my family now. I’ve been appreciating everything that they’ve done for me. I’m so happy that we’re finally together. And a long-term goal is to maybe have my own family someday.
Dr. Kahn: If you’re able to prevent relapses, you’re not only improving outcome overall, but you may actually be able to change the course of the illness.
Copy Super: In the United States, the median time between onset of first episode psychosis and treatment is over 18 months. That is 6 times longer than the World Health Organization guidelines. In a longitudinal cohort study, patients who initiated treatment within 3 months of first episode psychosis experienced half as many relapses after 2 years.
It Starts With a Spoonful
Explore the Clinical Insights Behind the Episode
Physiological Effects Following First-Episode Psychosis (FEP)
FEP in schizophrenia is an experience typically marked by crisis for patients and their families, as it often requires emergency assistance and hospitalization. Although many individuals can recover clinically and functionally after FEP, more than 80% of patients will experience subsequent relapses.1 These episodes of untreated psychosis may contribute to disabling cognitive and functional decline, from which patients cannot fully recover.2-6 Studies have demonstrated a loss of more than 1% of total brain volume—about a tablespoon—and a loss of up to 3% of grey matter volume within 1 to 2 years following FEP.7,8 This can exacerbate underlying cognitive impairments, negative symptoms, and lack of disease insight.3-5,9
Current treatment models focus predominantly on symptom control and remission maintenance.10 However, an emerging and more broadly coordinated approach to early intervention uses an extended range of treatment tools. These tools integrate treatment as usual along with family and peer education, employment counseling, and additional patient support to help individuals living with schizophrenia achieve a more sustained functional recovery.11-13
Loss of Brain Volume May Contribute to Cognitive Dysfunction in Schizophrenia
The clinical course of schizophrenia is typically characterized by a distinct, time-limited period of sharp deterioration. Current research suggests that this process may be influenced by neurodevelopmental abnormalities and progressive neuroanatomical deficits exacerbated by prolonged periods of untreated psychosis, particularly during early-phase illness.2,14,15
Active clinical deterioration proceeds rapidly during the late prodromal phase and in the weeks and months immediately after FEP, then continues at a slower pace throughout the first 5 to 10 years after FEP.2,15 Following the deterioration phase, most patients will transition into a chronic plateau phase, during which cognitive and psychosocial function remain relatively stable, although there may be subsequent exacerbations.2,5,14,15 However, increasing evidence indicates that multimodal, comprehensive intervention programs applied earlier and more consistently have the potential to fundamentally change the clinical trajectory of schizophrenia.11,16-18 Furthermore, initiating prompt pharmacological and psychosocial treatment for FEP patients may also help protect the brain from the irreversible neurologic harm caused by relapses and prolonged duration of untreated psychosis.3,19,20
Preservation and augmentation of cognitive function, rather than mere remission of psychotic symptoms, has increasingly become a core clinical objective within the larger mission to improve long-term outcomes.
References: 1. Robinson D, Woerner MG, Alvir JM, et al. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry. 1999;56(3):241-247. 2. Liberman JA, Perkins D, Belger A, et al. The early stages of schizophrenia: speculations on pathogenesis, pathophysiology, and therapeutic approaches. Biol Psychiatry. 2001;50(11):884-897. 3. Andreasen NC, Liu D, Ziebell S, Vora A, Ho BC. Relapse duration, treatment intensity, and brain tissue loss in schizophrenia: a prospective longitudinal MRI study. Am J Psychiatry. 2013;170(6):609-615. 4. Kim T, Lee KH, Oh H, et al. Cerebellar structural abnormalities associated with cognitive function in patients with first-episode psychosis. Front Psychiatry. 2018;9:286. 5. Kubota M, van Haren NEM, Haijma SV, et al. Association of IQ changes and progressive brain changes in patients with schizophrenia. JAMA Psychiatry. 2015;72(8):803-812. 6. Haynes VS, Zhu B, Stauffer VL, et al. Long-term healthcare costs and functional outcomes associated with lack of remission in schizophrenia: a post-hoc analysis of a prospective observational study. BMC Psychiatry. 2012;12:222. 7. Cahn W, Hulshoff Pol HE, Lems EBTE, et al. Brain volume changes in first-episode schizophrenia: a 1-year follow-up study. Arch Gen Psychiatry. 2002;59(11):1002-1010. 8. Cosgrove KP, Mazure CM, Staley JK. Evolving knowledge of sex differences in brain structure, function, and chemistry. Biol Psychiatry. 2007;62(8):847-855. 9. McKnight W. First-episode psychosis is a ‘brain attack,’ and LAIs can prevent recurrence, expert says. Clinical Psychiatry News. Published July 6, 2017. Accessed December 10, 2020. https://www.mdedge.com/psychiatry/article/141969/
schizophrenia-other-psychotic-disorders/first-episode-psychosis-brain. 10. Kahn RS, Sommer IE, Murray RM, et al. Schizophrenia. Nat Rev Dis Primers. 2015;1(15067):1-23.
11. Kane JM, Robinson DG, Schooler NR, et al. Comprehensive versus usual community care for first-episode psychosis: 2-year outcomes from the NIMH RAISE early treatment program. Am J Psychiatry. 2016;173(4):362-372. 12. Heinssen RK, Goldstein AB, Azrin ST. Evidence-based treatments for first episode psychosis: components of coordinated specialty care. National Institute of Mental Health. Published April 14, 2014. Accessed December 10, 2020. https://www.nimh.nih.gov/health/topics/schizophrenia/raise/
evidence-based-treatments-for-first-episode-psychosis-components-of-coordinated-specialty-care.shtml. 13. Petersen L, Jeppesen P, Thorup A, et al. A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness. BMJ. 2005;331(7517):602. 14. McGlashan TH. Is active psychosis neurotoxic? Schizophr Bull. 2006;32(4):609-613. 15. Drake RJ, Husain N, Marshall M, et al. Effect of delaying treatment of first-episode psychosis on symptoms and social outcomes: a longitudinal analysis and modelling study. Lancet Psychiatry. 2020;7:602-610. 16. Nossel I, Wall MM, Scodes J, et al. Results of a coordinated specialty care program for early psychosis and predictors of outcomes. Psychiatr Serv. 2018;69(8):863-870. 17. Gleeson JFM, Cotton SM, Alvarez-Jimenez M, et al. A randomized controlled trial of relapse prevention therapy for first-episode psychosis patients: outcome at 30-month follow-up. Schizophr Bull. 2013;39(2):436-448. 18. Correll CU, Galling B, Pawar A, et al. Comparison of early intervention services vs treatment as usual for early-phase psychosis: a systematic review, meta-analysis, and meta-regression. JAMA Psychiatry. 2018;75(6):555-565. 19. Wyatt RJ. Neuroleptics and the natural course of schizophrenia. Schizophr Bull. 1991;17(2):325-351. 20. Stahl SM. Long-acting injectable antipsychotics: shall the last be first? CNS Spectr. 2014;19(1):3-5.
Decline Is Not Inevitable
3 leading psychiatrists discuss how a coordinated specialty care paradigm can help improve long-term outcomes.
Human Impact of
This interactive tool explores the widespread effects of relapse and ways to remediate them.
A New Standard Emerges
Recent landmark studies support the wide adoption of coordinated specialty care.
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